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Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the main cause of chronic liver disease in children and adolescents. Indeed, epidemiological studies have shown that MASLD affects up to 40% of children with obesity. Despite the recent approval of medications that target weight loss in adolescents that could have benefits on pediatric MASLD, lifestyle interventions, such as diet and exercise, remain the mainstay of our therapeutic approach. More specifically, studies on diet alone have focused on the possible role of carbohydrate or fat restriction, albeit without a definite answer on the best approach. Weight loss after dietary intervention in children with obesity and MASLD has a beneficial effect, regardless of the diet used. In relation to the role of exercise in MASLD reversal, indirect evidence comes from studies showing that a sedentary lifestyle leading to poor fitness, and low muscle mass is associated with MASLD. However, research on the direct effect of exercise on MASLD in children is scarce. A combination of diet and exercise seems to be beneficial with several studies showing improvement in surrogate markers of MASLD, such as serum alanine aminotransferase and hepatic fat fraction, the latter evaluated with imaging studies. Several dietary supplements, such as vitamin E, probiotics, and omega-3 fatty acid supplements have also been studied in children and adolescents with MASLD, but with equivocal results. This review aims to critically present available data on the effects of lifestyle interventions, including diet, exercise, and dietary supplements, on pediatric MASLD, thus suggesting a frame for future research that could enhance our knowledge on pediatric MASLD management and optimize clinicians' approach to this vexing medical condition., (© 2024. The Author(s).)

Background: Follistatin-like protein 1 (FSTL1) has been identified as a secreted glycoprotein that plays an important role in obesity. However, its role in children with metabolic-associated fatty liver disease (MAFLD) has not been investigated. This study aimed at characterizing the relationship between serum FSTL1 concentration and MAFLD in children with obesity., Methods: A total of 121 subjects were recruited from the Second Affiliated Hospital of Xi'an Jiaotong University, including 45 obese children with MAFLD, 31 obese children without MAFLD, and 45 healthy controls. Anthropometric parameters, biochemical data were measured and circulating FSTL1 levels were detected by ELISA., Results: The levels of FSTL1 in obese children with MAFLD were higher than that in obese children without MAFLD: 1.31 (0.35-2.29) ng/mL vs. 0.55 (0.36-1.38) ng/mL. Correlation analysis illustrated that FSTL1 was associated with nonesterified free fatty acid and leptin (r = 0.278, P < 0.05 and r = 0.572, P < 0.05, respectively). Binary logistic regression suggested that increased FSTL1 was a risk factor for MAFLD in children (OR = 1.105, 95% CI: 1.066-1.269, P < 0.05)., Conclusions: Serum FSTL1 concentrations increase in obese children with MAFLD and may have the potential to be a risk factor for MAFLD in children with obesity., (© 2024. The Author(s).)

Background: Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD., Methods: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored., Results: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045)., Conclusion: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children., Trial Registration: The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023)., (© 2024. The Author(s).)

Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Inflammation is involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). The monocyte to high-density lipoprotein cholesterol ratio (MHR) has emerged as a marker for various inflammation-related diseases. The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity., Methods: Based on hepatic ultrasound, a total of 504 children with obesity (357 with NAFLD and 147 without NAFLD) were included in the study. The correlation between the MHR and NAFLD risk factors was assessed by Pearson's and Spearman's analyses. Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD., Results: The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD [0.52 (0.44-0.67) versus 0.44 (0.34-0.57), P<0.001]. Multivariate stepwise logistic regression analysis demonstrated that the MHR [odds ratio (OR): 1.033, 95% confidence interval (CI): 1.015-1.051; P<0.001] was an independent predictor of NAFLD in childhood obesity patients, as were age (OR: 1.205, 95% CI: 1.059-1.371; P=0.005], waist circumference [OR: 1.037, 95% CI: 1.008-1.067; P=0.012], and alanine transaminase [OR: 1.067, 95% CI: 1.045-1.089; P<0.001]. Additionally, MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors., Conclusion: The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity., (© 2024. Huazhong University of Science and Technology.)

Background: Nonalcoholic fatty liver disease (NAFLD) has become an important health issue in adolescents. Although several parameters and indices have been investigated for the evaluation of NAFLD in adults, these indices are limited in adolescents. In this study, body mass index, waist circumference, triponderal mass index, HbA1c, homeostatic model assessment insulin resistance (HOMA-IR), triglyceride/high-density lipoprotein (Tg/HDL), the lipid accumulation product (LAP) index, the triglyceride-glucose (TyG) index and the aminotransferase (AT) index were examined together, and their diagnostic values in the clinical treatment of NAFLD were compared., Materials and Methods: Seventynine adolescents (10-19 years old) with obesity who were admitted to a pediatric clinic between January and August 2022 and who were diagnosed with exogenous obesity without any comorbidities were included in the study. The presence of NAFLD was evaluated by liver magnetic resonance imaging. The laboratory findings were obtained retrospectively from system records. Parameters were compared between the NAFLD (+) and NAFLD (-) groups. Logistic regression analysis was used to determine the most effective factors for NAFLD treatment. Receiver operating characteristic (ROC) analysis was performed with significant indices. Sex, HOMA-IR, TyG and AT indices were evaluated together with multivariate analysis to design a diagnostic scale., Results: HbA1c, HOMA-IR, AT indices and TyG indices were greater in the NAFLD (+) group (P = 0.012; P = 0.001; P = 0.012; P = 0.002, respectively). There was a positive correlation between liver fat percentage and HOMA-IR, the TyG index, the AT index, and Tg/HDL. According to the regression analysis, male sex and elevated HOMA-IR were determined to be significant risk factors for the presence of NAFLD. A probability scale with 4 parameters [sex, HOMA-IR, the TyG index, and alanine aminotransferase (ALT)] was designed with 82.5% specificity and 80% sensitivity., Conclusion: Evaluation of the HOMA-IR and TyG indices, especially in high-risk patients, will support the diagnosis of NAFLD via ultrasonography. A probability scale with ALT, HOMA-IR, TyG, and sex data with a diagnostic accuracy of 80% may aid in the diagnosis of NAFLD in adolescents with obesity., (© 2024. The Author(s).)

Introduction: Parallel to the worldwide increase in obesity, the epidemic of chronic liver disease is increasing also in pediatric population. Our aim is to provide a different outlook on the current screening confusion in pediatric non-alcoholic fatty liver disease (NAFLD) with the non-invasive vibration-controlled transient elastography (VCTE) method., Materials and Methods: This single-center, cross-sectional, comparative study was performed at the tertiary center, included 95 patients with obesity and 116 controls, both groups were 9-18 years of ages. VCTE examinations performed in all patients. The cut-off values for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were established by comparing the study and control groups., Results: The cut-off for CAP was determined as >236 dB/m when comparing the two groups. The AUC was 0.900 (95% CI, 0.851-0.937) and the diagnostic accuracy was 77.9% and 91.4% for sensitivity and specificity, respectively. The cut-off value for LSM >5 kPa was determined by comparison of the two groups. The AUC was 0.794 (95% CI, 0.733-0.846) and the diagnostic accuracies were 50.5% and 90.5% for sensitivity and specificity, respectively., Conclusions: There is no benchmark method for screening pediatric NAFLD. However, VCTE is a promising method for screening pediatric NAFLD. It is accessible, repeatable and practical., (© 2024 Wiley Periodicals LLC.)

Objectives: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses., Methods: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia., Results: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels., Conclusions: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status., (Copyright © 2024. Published by Elsevier Ltd.)

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children. Like adults, children can develop the progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), which is characterized by hepatic inflammation, often in the presence of fibrosis. Children with NAFLD are at higher risk of liver-related complications, metabolic dysfunction, and cardiovascular disease in adulthood. Many factors contribute to the escalating prevalence of NAFLD in the pediatric population, among which are an array of dietary patterns such as overnutrition, poor diet quality, and heavy consumption of fat and sugar, including fructose. Findings from an increasing number of epidemiological studies support a connection between high habitual sugar consumption and NAFLD, especially within the context of obesity, but these studies are not able to demonstrate whether sugar is a contributing factor or instead an indicator of an overall poor diet (or lifestyle) quality. To date, only four randomized controlled dietary interventions assessing the effects of sucrose/fructose restriction on hepatic fat fraction in youth with obesity have been published. The objectives of this review are to summarize the key findings from these dietary interventions to achieve a better understanding of the strength of the relationship between dietary sugar restriction and liver fat reduction, despite their inherent limitations, and to discuss the potential impact of weight loss and fat mass reduction on improvement in hepatic steatosis.

Objectives: Non-alcoholic fatty liver disease (NAFLD) has significant genetic susceptibility. Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis. However, the association between adipocytokine pathway genes and NAFLD remains unclear. This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children., Methods: A case-control study was conducted, dividing obese children into NAFLD and control groups. Peripheral venous blood (2 mL) was collected from each participant for DNA extraction. A total of 14 single nucleotide polymorphisms (SNP) in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing. Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children. Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression. Generalized multifactor dimensionality reduction (GMDR) was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children., Results: A total of 1 022 children were included, with 511 in the NAFLD group and 511 in the control group. After adjusting for age, gender, and BMI, multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models: heterozygote model (CG vs CC, OR =0.58, 95% CI 0.36 to 0.95, P =0.029), dominant model (GG+CG vs CC, OR =0.62, 95% CI 0.38 to 1.00, P =0.049), and overdominant model (CC+GG vs CG, OR =1.72, 95% CI 1.06 to 2.80, P =0.028). PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models: heterozygous model (CT vs CC, OR =1.51, 95% CI 1.10 to 2.07, P =0.011), dominant model (CT+TT vs CC, OR =1.50, 95% CI 1.10 to 2.03, P =0.010), overdominant model (CC+TT vs CT, OR =0.67, 95% CI 0.49 to 0.92, P =0.012), and additive model (CC vs CT vs TT, OR =1.40, 95% CI 1.07 to 1.83, P =0.015). No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD. GMDR analysis, adjusted for age, gender, and BMI, revealed no statistically significant interactions among the 14 SNPs (all P >0.05)., Conclusions: Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children. However, no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.

Background: Weight loss and lifestyle interventions are the mainstay of treatment in pediatric NAFLD. There are gaps in the literature on the objective improvement in BMI to meaningfully impact NAFLD in children., Aim: To determine the decrease in BMI associated with a significant decline in ALT and other metabolic parameters., Methods: Retrospective chart review of pediatric patients with the diagnosis of NAFLD. Data were collected at the baseline and 6 and 12 months. A linear regression model was used to assess the percent change in BMI predictive of change in ALT and other metabolic parameters., Results: 281 charts were included. 71% of patients who had up to a 2.5% loss in BMI at 6 months had a decrease in ALT of up to 10 U/L compared to 43% patients who did not have a decrease in BMI up to 2.5% loss at the same time period ( P =0.01). The linear regression model showed that 6-month and 12-month percent changes in BMI are predictive of 6-month and 12-month ALT changes ( P =0.01 and 0.02), respectively. ALT normalization was achieved on 12% of patients with a ≥2.5% decrease in BMI at 6 months compared to 1% of patients that had no decrease of ≥2.5% decrease in BMI at 6 months ( P =0.01). The mean BMI Z -score decline was 0.18 ( P =0.001) in the group with a ≥2.5% decrease in BMI at 6 months., Conclusions: BMI loss of up to 2.5% and the mean BMI Z-score 0.18 are associated with a significant decrease in ALT of up to 10 U/L. BMI percent change at 6 months and 12 months is predictive of changes in ALT. These results should help guide providers in clinical practice set objective goals for the management of children with NAFLD resulting from obesity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Alvaro G. Flores Lopez et al.)

Objectives: Controlled attenuation parameter (CAP) is a noninvasive and quantitative method to evaluate hepatic steatosis, which is not well evaluated in children. The aim of this study was to examine the diagnostic value of CAP for hepatic steatosis in children with obesity based on MR proton density fat fraction (PDFF)., Methods: About 108 pediatric patients with nonalcoholic fatty liver disease (NAFLD) who were assessed for PDFF, CAP, and other laboratory results were enrolled. In this study, pediatric patients were separated for the obese group (n=80) and the severe obese group (n=28). Hepatic steatosis grades (0-3) were classified according to PDFF using cutoff values of 6.4 , 17.4, and 22.1 %., Results: There are significant differences in CAP between the obese and severe obese groups (p<0.05). CAP showed a good correlation with PDFF in pediatric patients with NAFLD for diagnosing hepatic steatosis using a cutoff value of 265 dB/m (p<0.001). Meanwhile, ALT significantly outperforms CAP in receiver-operating curve (ROC) analysis for diagnosing hepatic steatosis grades. The diagnostic accuracy of CAP for steatosis is 77.8 %, and the diagnostic accuracy of ALT for steatosis is 83.3 %., Conclusions: While CAP holds promise as a diagnostic tool for pediatric NAFLD, its diagnostic performance warrants some caution. The potential of CAP is evident; however, ALT emerges as a simpler and more accurate measure for detecting hepatic steatosis in children. Further research is essential to determine the optimal role of CAP in pediatric NAFLD diagnosis and management., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Introduction: Stromal cell-derived factor-1 (SDF-1) is a newly discovered small molecule adipocytokine, and research has shown that it is closely related to the occurrence and development of obesity. However, there are currently few research reports on SDF-1 in childhood obesity and nonalcoholic fatty liver disease (NAFLD), and this study aims to explore the relationship between SDF-1 and obesity related indicators in obese children., Methods: Serum SDF-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and biochemical data were collected, such as body mass index (BMI), waist and hip circumference, blood pressure, liver enzymes, cholesterol, and fasting insulin. Children with NAFLD or not were evaluated through Color Doppler Ultrasound., Results: Serum SDF-1 concentrations were significantly higher in obese subjects than in non-obese subjects (P < 0.05), and were elevated in the NAFLD obese subjects than in the non-NAFLD obese subjects (P < 0.05). SDF-1 was positively correlated with BMI, waist-to-hip ratio, systolic blood pressure, body fat percentage (BFP), basal metabolic rate (BMR), alanine transaminase (ALT), aspartate transaminase (AST), glutyltranspeptidase (GT), and homoeostasis model of HOMA-IR, independent of their uric acid (UA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), gender and age. BFP and BMR were associated with the serum SDF-1 concentrations in multivariable linear regression analysis., Conclusion: These results suggest that SDF-1 levels are elevated in obese children and are associated with NAFLD, indicating that SDF-1 may play a role in the development of childhood obesity and metabolic disorders., (© 2024. The Author(s).)

Objectives: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in overweight and obese children, and its etiology and pathogenesis remain unclear, lacking effective preventive and therapeutic measures. This study aims to explore the association between whole blood copper, zinc, calcium, magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years, providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children., Methods: A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys. Fasting blood samples were collected from the subjects, and various indicators such as blood glucose, blood lipid, and mineral elements were detected. All children were divided into an overweight group ( n =400) and a NAFLD group ( n =202). The NAFLD group was divided into 2 subgroups according to the ALT level: A non-alcoholic fatty liver (NAFL) group and a non-alcoholic steatohepatitis (NASH) group. Logistic regression analysis was used to analyze the association between minerals (copper, zinc, calcium, magnesium, and iron) and NAFLD, NAFL and NASH., Results: A total of 602 subjects were included, of whom 73.6% were male, with a median age of 10 (9, 11) years, and a body mass index (BMI) of 24.9 (22.7, 27.4) kg/m 2 . The intergroup comparison results showed that compared with the overweight group, the NAFLD group had higher levels of age, BMI, diastolic blood pressure (DBP), systolic blood pressure (SBP), triglyceride (TG), low density lipoprotein (LDL), alanine transaminase (ALT) and aspartate aminotransferase (AST), and lower level of high density lipoprotein (HDL). The NAFL group had higher levels of age, BMI, DBP, SBP, ALT, and AST, and lower levels of HDL compared with the overweight group. The levels of age, BMI, DBP, SBP, TG, LDL, ALT, and AST of NASH were higher than those in the overweight group, while the level of HDL was lower than that in overweight group (all P <0.017). After adjusting for a variety of confounders, the OR of NAFLD for the highest quantile of iron was 1.79 (95% CI 1.07 to 3.00) compared to the lowest quantile, and no significant association was observed between copper, zinc, calcium, and magnesium, and NAFLD. The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21 (95% CI 1.26 to 3.88), while no significant association was observed between iron level and NASH. In addition, no significant associations were observed between copper, zinc, calcium, and magnesium levels and NAFL or NASH., Conclusions: High iron level increases the risk of NAFLD (more likely NAFL) in overweight and obese children, while copper, zinc, calcium, magnesium, and other elements are not associated with the risk of NAFLD in overweight and obese children.

NAFLD has become the leading cause of chronic liver disease in children, as a direct consequence of the high prevalence of childhood obesity. This study aimed to characterize body composition trajectories from childhood to adolescence and their association with the risk of developing nonalcoholic fatty liver disease (NAFLD) during adolescence. The participants were part of the 'Chilean Growth and Obesity Cohort Study', comprising 784 children who were followed prospectively from age 3 years. Annual assessments of nutritional status and body composition were conducted, with ultrasound screening for NAFLD during adolescence revealing a 9.8% prevalence. Higher waist circumference measures were associated with NAFLD from age 3 years ( p = 0.03), all skin folds from age 4 years ( p < 0.01), and DXA body fat measurements from age 12 years ( p = 0.01). The fat-free mass index was higher in females ( p = 0.006) but not in males ( p = 0.211). The second and third tertiles of the fat mass index (FMI) had odds ratios for NAFLD during adolescence of 2.19 (1.48-3.25, 95% CI) and 6.94 (4.79-10.04, 95% CI), respectively. Elevated waist circumference, skin folds, and total body fat were identified as risk factors for future NAFLD development. A higher FMI during childhood was associated with an increased risk of NAFLD during adolescence.

Sleep is a factor associated with overweight/obesity risk, wherein interactions with fatty liver should be ascertained. The aim of this cross-sectional study was to analyze the possible relationships of sleep with liver health and whether this interplay is related to body adiposity distribution in children and adolescents. Anthropometric, clinical, and biochemical measurements were performed in children and adolescents (2-18 years old) with overweight/obesity (n = 854). Body fat distribution was clinically assessed, and several hepatic markers, including hepatic steatosis index, were calculated. Sleep time mediation (hours/day) in the relationship between the hepatic steatosis index and body fat distribution was investigated. Differences among diverse fatty liver disease scores were found between children with overweight or obesity (p < 0.05). Linear regression models showed associations between hepatic steatosis index and lifestyle markers (p < 0.001). Hepatic steatosis index was higher (about + 15%) in children with obesity compared to overweight (p < 0.001). Pear-shaped body fat distribution may seemingly play a more detrimental role on liver fat deposition. The association between sleep time and hepatic steatosis index was dependent on body mass index z-score. Post hoc analyses showed that 39% of the relationship of body fat distribution on hepatic steatosis index may be explained by sleep time.  Conclusion: An association of sleep time in the relationship between body fat distribution and hepatic steatosis index was observed in children and adolescents with overweight/obesity, which can be relevant in the prevention and treatment of excessive adiposity between 2 and 18 years old., Clinical Trial: NCT04805762.    Import: As part of a healthy lifestyle, sleep duration might be a modifiable factor in the management of fatty liver disease in children., What Is Known: • Sleep is an influential factor of overweight and obesity in children. • Excessive adiposity is associated with liver status in children and adolescents., What Is New: • Sleep time plays a role in the relationship between body fat distribution and liver disease. • Monitoring sleep pattern may be beneficial in the treatment of hepatic steatosis in children with excessive body weight., (© 2023. The Author(s).)

Introduction: Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible., Methods and Analysis: This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12-18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study's feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome., Ethics and Dissemination: This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals., Clinicaltrials: gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023., Trial Registration Number: NCT03994029., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Data sources for assessing pediatric chronic diseases and associated screening practices are rare. One example is non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease prevalent among children with overweight and obesity. If undetected, NAFLD can cause liver damage. Guidelines recommend screening for NAFLD using alanine aminotransferase (ALT) tests in children ≥9 years with obesity or those with overweight and cardiometabolic risk factors. This study explores how real-world data from electronic health records (EHRs) can be used to study NAFLD screening and ALT elevation. Research Design: Using IQVIA's Ambulatory Electronic Medical Record database, we studied patients 2-19 years of age with body mass index ≥85th percentile. Using a 3-year observation period (January 1, 2019 to December 31, 2021), ALT results were extracted and assessed for elevation (≥1 ALT result ≥22.1 U/L for females and ≥25.8 U/L for males). Patients with liver disease (including NAFLD) or receiving hepatotoxic medications during 2017-2018 were excluded. Results: Among 919,203 patients 9-19 years of age, only 13% had ≥1 ALT result, including 14% of patients with obesity and 17% of patients with severe obesity. ALT results were identified for 5% of patients 2-8 years of age. Of patients with ALT results, 34% of patients 2-8 years of age and 38% of patients 9-19 years of age had ALT elevation. Males 9-19 years of age had a higher prevalence of ALT elevation than females (49% vs. 29%). Conclusions: EHR data offered novel insights into NAFLD screening: despite screening recommendations, ALT results among children with excess weight were infrequent. Among those with ALT results, ALT elevation was common, underscoring the importance of screening for early disease detection.

Background and Aim: Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in adolescent and adult population. However, the epidemiologic data of MAFLD in prepubertal children remain limited. This study aimed to investigate the prevalence and incidence of MAFLD and assess the role of anthropometric parameters in identifying and predicting MAFLD in this population., Methods: Children from the Shanghai Birth Cohort Study who underwent an 8-year follow-up with anthropometric measurements and transient elastography FibroScan-502 examination (M probe, Echosens, Paris, France) were enrolled. Some of them also completed a 5-year follow-up. Diagnosis of fatty liver disease (FLD) was based on the controlled attenuation parameter (CAP) value exceeding 248 dB/m, and MAFLD was defined as FLD combined with obesity or central obesity. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of anthropometric parameters for MAFLD., Results: A total of 848 children (431 boys) from the Shanghai Birth Cohort Study were followed up for 8 years, and among them, 385 children (189 boys) also participated in the 5-year follow-up. The prevalence of FLD and MAFLD at 5 years old was 3.90% and 0.52%, respectively, while at 8 years old, the prevalence rates increased to 5.07% for FLD and 3.42% for MAFLD. The 8-year-old children with MAFLD exhibited significantly higher weight, body mass index (BMI), chest circumference, waist circumference, hip circumference, waist-to-height ratio, waist-to-hip ratio, and liver stiffness measurement compared to those without MAFLD (all p < 0.05). The incidence rates of FLD and MAFLD at 8 years old, considering the 5-year follow-up data, were 3.78% (14/370) and 3.13% (12/383), respectively. Obese or centrally obese children at 5 years old had a higher incidence of FLD and MAFLD at the 8-year follow-up. Waist circumference and BMI showed significant associations with the presence and incidence of MAFLD, respectively, with the largest AUC values in ROC curve analysis. In addition, chest circumference was significantly associated with MAFLD in obese children., Conclusion: This study provides insights into the incidence and prevalence of MAFLD in prepubertal children. It underscores the importance of anthropometric parameters in identifying and predicting MAFLD in this population. Further research encompassing a broader age range and incorporating these indicators and additional metabolic markers is necessary to enhance the understanding and management of MAFLD in children., (© 2023. Asian Pacific Association for the Study of the Liver.)

Currently, most predictions of metabolic-associated fatty liver disease (MAFLD) in school-aged children utilize indicators that usually predict nonalcoholic fatty liver disease (NAFLD). The present study aimed to develop new predictive models and predictors for children with MAFLD, which could enhance the feasibility of MAFLD screening programs in the future. A total of 331 school-aged overweight/obese children were recruited from six primary schools in Ningbo city, China. Hepatic steatosis and fibrosis were detected with controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Machine learning methods were adapted to build a set of variables to predict MAFLD in children. Then, the area under the curve (AUC) of multiple models and indices was compared to predict pediatric MAFLD. Compared with non-MAFLD children, children with MAFLD had more obvious metabolic disturbances, as they had higher anthropometric indicators, alanine aminotransferase, fasting plasma glucose, and inflammation indicators (white blood cell count, hemoglobin, neutrophil count) (all P < 0.05). The optimal variables for all subjects selected by random forest (RF) were alanine aminotransferase, uric acid, insulin, and BMI. The logistic regression (LR) model performed best, with AUC values of 0.758 for males and 0.642 for females in predicting MAFLD. LnAI-BMI, LnAI, and LnAL-WHtR were approving indices for predicting pediatric MAFLD in all participants, boys and girls individually., Conclusions: This study developed LR models and sex-specific indices for predicting MAFLD in overweight/obese children that may be useful for widespread screening and identification of children at high risk of MAFLD for early treatment., What Is Known: • Most of the indicators predicting pediatric MAFLD are derived from the predictive indicators for NAFLD, but the diagnostic criteria for MAFLD and NAFLD are not exactly the same. • The accuracy of predictors based on routine physical examination and blood biochemical indicators to diagnose MAFLD is limited., What Is New: • This study developed indicators based on routine examination parameters that have approving performance for MAFLD, with AUC values exceeding 0.70., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Obesity in adolescence is associated with significant morbidity and predisposes adolescents to the development of cardiovascular disease (CVD). Although a number of traditional CVD risk factors have been identified in youth, limited data exist regarding non-traditional CVD risk factors. In 89 adolescents with metabolic syndrome (MetS), with 60 age-, gender-, and BMI-matched controls, we determined the non-traditional CVD risk factors (hs-CRP, TG/HDL ratio, ApoB/ApoA1 ratio, NAFLD) in order to investigate whether they may be used as biomarkers for predicting future CVD, and we evaluated their response to the implementation of a multidisciplinary, personalized, lifestyle intervention program for 1 year. We demonstrated that the TG/HDL ratio, IL-2, IL-6, IL-17A, and INF-γ were significantly increased in subjects with MetS than in controls, and may be used as biomarkers to predict future CVD. Subjects with MetS had an increased mean carotid intima-media thickness (cIMT) and prevalence of NAFLD than the controls, while the prevalence of NAFLD correlated strongly with cIMT and IL-6 concentrations. Most of the non-traditional cardiovascular risk factors improved following the implementation of a lifestyle intervention program. These findings indicate that adolescents with MetS may have a greater risk for developing atherosclerosis early in life, while early lifestyle intervention is crucial for preventing the arteriosclerotic process in youth.

Objectives: Metabolic syndrome (MetS) is a cluster of conditions linked to obesity that increases cardiovascular risk. We evaluated the frequency of clinical abnormalities associated with overweight and obesity in childhood, to determine whether a diagnosis of MetS is appropriate in this population., Methods: Cross-sectional study with 116 pubertal and prepubertal children with a mean age (SD) of 10.9 (2.5) years, with overweight and obesity. We defined MetS using the International Diabetes Federation criteria, regardless of the age., Results: 45 patients met the criteria, 20 had at least one metabolic abnormality in addition to a high waist circumference (WC), and seven with WC below percentile 90th, had at least one metabolic abnormality. The prepubertal had higher zBMI [3.1 (2.6-3.8) vs. 2.8 (2.4-3.3); p=0.037], less lean body mass (kg) [27.13 (7.3) vs. 34.13 (9.8); p=0.005] and a similar frequency of non-alcoholic fatty liver disease (NAFLD) compared to the pubertal [44.7 vs. 35.9; p=0.323]. Prepubertal with NAFLD had higher zBMI, lower HDL levels, higher TG/HDL ratios and higher fat percentages; while pubertal with NAFLD had higher WC/height, aspartate aminotransferase and oxaloacetic transaminase., Conclusions: The diagnosis of MetS in childhood is not fundamental. Individualized management, focusing on the earliest age groups, in which we identified a more severe degree of obesity, should be done. We also recommend screening for NAFLD in all ages, due to the high prevalence observed., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: The prevalence of childhood obesity increases globally, and noninvasive methods are needed to identify metabolic dysfunction and obesity-related complications such as pediatric metabolic associated fatty liver disease (MAFLD). We investigated whether uric acid (UA) and the macrophage marker soluble form of cysteine scavenger receptor CD163 (sCD163) can be used as biomarkers for deteriorated metabolism or pediatric MAFLD in children with overweight or obesity., Methods: Cross-sectional clinical and biochemical data from 94 children with overweight or obesity was included. Surrogate liver markers were calculated, and correlations were investigated using Pearson's or Spearman's correlation test., Results: UA and sCD163 correlated with BMI standard deviation score (r=0.23, p<0.05; r=0.33, p<0.01) and body fat (r=0.24, p<0.05; r=0.27, p=0.01). UA correlated with triglycerides (ρ=0.21, p<0.05), fat free mass (r=0.33, p<0.01), and gamma-glutamyl transferase (r=0.39, p<0.01). sCD163 correlated with the pediatric NAFLD fibrosis score (r=0.28, p<0.01) and alanine aminotransferase (r=0.28, p<0.01). No correlation was found between UA and pediatric MAFLD., Conclusions: UA and sCD163 was identified as markers of a deranged metabolic profile, thus acting as easily accessible biomarkers for obesity and an obesity-related deranged metabolism. Furthermore, increasing levels of sCD163 could be a useful biomarker of pediatric MAFLD. Future prospective studies are warranted., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children., Methods: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH., Results: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH ( P <0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95% CI : 0.613-0.694), and for NASH (area under the curve: 0.771, 95% CI : 0.723-0.819)., Conclusions: The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.

Introduction: The prevalence of obesity constantly increases worldwide and definitely increases the risk of premature death in early adulthood. While there is no treatment yet with proven efficacy for the metabolic clamp such as arterial hypertension, dyslipidemia, insulin resistance, diabetes type 2, and fatty liver disease, it is imperative to find a way to decrease cardiometabolic complications. Early prevention strategies beginning in childhood are the most logical step to reduce future cardiovascular morbidity and mortality. Therefore, the aim of the current study is to determine the most sensitive and specific predictive markers of the metabolically unhealthy phenotype with high cardiometabolic risk in overweight/obese adolescent boys., Methods: This study was carried out at the Ternopil Regional Children's hospital (Western Ukraine) and involved 254 randomly chosen adolescent overweight or obese boys [median age was 16.0 (15.0,16.1) years]. A control group of 30 healthy children with proportional body weight comparable in gender and age to the main group was presented. A list of anthropometrical markers with biochemical values of carbohydrate and lipid metabolism with hepatic enzymes was determined. All overweight/obese boys were divided into three groups: 51.2% of the boys with metabolic syndrome (MetS) based on the IDF criteria; 19.7% of the boys were metabolically healthy obese (MHO) without hypertension, dyslipidemia, and hyperglycemia; and the rest of the boys (29.1%) were classified as metabolically unhealthy obese (MUO) with only one criterion (hypertension, dyslipidemia, or hyperglycemia)., Results: Based on multiple logistic regression analysis that included all anthropometric and biochemical values and calculated indexes in boys from the MHO group and MetS, it was revealed that the maximum likelihood in the prediction of MetS makes the combination of triglyceride glucose index, pediatric nonalcoholic fatty liver disease fibrosis index (PNFI), and triglyceride-to-high-density lipoprotein cholesterol ratio (R 2 =0.713, p<0.000). By tracing the receiver operating characteristic curve, the model is confirmed as a good predictor of MetS (AUC=0.898, odds ratio=27.111 percentage correct=86.03%) in overweight and obese boys., Conclusion: Triglyceride glucose index, pediatric NAFLD fibrosis index, and triglyceride-to-high-density lipoprotein cholesterol ratio are a valuable combination of predictive markers of the metabolically unhealthy phenotype in Ukrainian overweight/obese boys., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Furdela, Pavlyshyn, Shulhai, Kozak and Furdela.)

Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions worldwide. Moreover, the prevalence of this liver disease is expected to increase rapidly in the near future, aligning with the rise in obesity and the aging of the population. The pathogenesis of NAFLD is considered to be complex and to include the interaction between genetic, metabolic, inflammatory, and environmental factors. It is now well documented that NAFLD is linked to the other conditions common to insulin resistance, such as abnormal lipid levels, metabolic syndrome, and type 2 diabetes mellitus. Additionally, it is considered that the insulin resistance may be one of the main mechanisms determining the disturbances in both bone tissue metabolism and skeletal muscles quality and functions in patients with NAFLD. To date, the association between NAFLD and osteoporosis has been described in several studies, though it worth noting that most of them included postmenopausal women or elderly patients and originated from Asia. However, taking into account the health and economic burdens of NAFLD, and the increasing prevalence of obesity in children and adolescents worldwide, further investigation of the relationship between osteopenia, osteoporosis and sarcopenia in NAFLD, including in young and middle-aged patients, is of great importance. In addition, this will help to justify active screening and surveillance of osteopenia and osteoporosis in patients with NAFLD. In this review, we will discuss various pathophysiological mechanisms and possible biologically active molecules that may interplay between NAFLD and bone tissue metabolism.

Non-alcoholic fatty liver disease (NAFLD) represents a complex chronic condition, which in the absence of screening-monitoring markers and effective standardized treatment is one of the most important issues in pediatric pathology. In this study, we analyzed the role of vitamin D supplementation in obese children with/without NAFLD and the impact on the components of the associated metabolic syndrome (MS). The study included 22 children with simple obesity (SO) and 50 with NAFLD, aged between 6 and 14 years, who received regimen-based therapy or vitamin D supplementation in case of deficiency. Anthropometric and paraclinical data associated with MS were statistically compared before and after treatment. It was observed that there was a statistical association of NAFLD with MS components, which were present both in SO and in the 6-9 years group. Vitamin D deficiency was associated with the presence of obesity, NAFLD and MS components, and correction of the deficiency induced a tendency to normalize the associated parameters. In the case of a treatment strictly based on the regimen, we found decreases in vitamin D values and additional alteration of some parameters. Supplementation with vitamin D potentiates the effects of the specific regimen, and the effects seem to be dependent on the MS components.

As in adults, childhood obesity is associated with several metabolic disorders; however, there is little information regarding complex obesity-derived complications such as hepatic steatosis or endothelial dysfunction at early ages. Therefore, the objective of the present study was to analyze the effect of a nutritional and physical exercise program on obesity comorbidities in the form of subclinical atherosclerosis and non-alcoholic fatty liver in young children. A total of 148 children completed the study. For nine months (one academic year), children carried out a nutritional and physical activity program of 3 h/week. Anthropometric, clinical, liver ultrasound and carotid intima-media thickness (cIMT) parameters were evaluated. Our results showed that the program significantly improved anthropometrical parameters, especially regarding BMI and body fat ( p < 0.001 and p = 0.004, respectively). The effect on metabolic parameters was limited, although a significant reduction on triglycerides was observed ( p = 0.009). The education program had a great influence on the echogenic parameters, since the percentage of children with light steatosis decreased from 35% to 4% at the end of the study. In addition, cIMT also decreased significantly in both groups, although there was no statistically significant differences between groups. In conclusion, detection of early complications of obesity through sonographic parameters may allow early intervention, as in the present study, to prevent obesity co-morbidities in children.

Background: While linked to obesity and associated with an increased cardiovascular morbidity, non-alcoholic fatty liver disease (NAFLD) is an often-asymptomatic cause of chronic liver disease in children. Early detection provides opportunity for interventions to curb progression. Childhood obesity is on the rise in low/middle-income countries, but cause-specific mortality data associated with liver disease are scanty. Establishing the prevalence of NAFLD in overweight and obese Kenyan children would guide in public health policies aimed at early screening and intervention., Objectives: To investigate prevalence of NAFLD in overweight and obese children aged 6-18 years using liver ultrasonography., Methodology: This was a cross-sectional survey. After obtaining informed consent, a questionnaire was administered, and blood pressure (BP) measured. Liver ultrasonography was performed to assess fatty changes. Categorical variables were analysed using frequency and percentages. χ 2 test and multiple logistic regression model were used to determine relationship between exposure and outcome variables., Results: Prevalence of NAFLD was 26.2% (27/103, 95% CI=18.0% to 35.8%). There was no association between sex and NAFLD (OR1.13, p=0.82; 95% CI=0.4 to 3.2). Obese children were four times more likely to have NAFLD compared with overweight children (OR=4.52, p=0.02; 95% CI=1.4 to 19.0). About 40.8% (n=41) had elevated BP, but there was no association with NAFLD (OR=2.06; p=0.27; 95% CI=0.6 to 7.6). Older children (13-18 years) were more likely to have NAFLD (OR 4.42; p=0.03; 95% CI=1.2 to 17.9)., Conclusion: Prevalence of NAFLD was high in overweight and obese school children in Nairobi. Further studies are needed to identify modifiable risk factors to arrest progression and prevent sequelae., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Relative enhancement (RE) in gadoxetate disodium (Gd-EOB-DTPA)-enhanced MRI is a reliable, non-invasive method for the evaluation and differentiation between simple steatosis and non-alcoholic steatohepatitis in adults. This study evaluated the diagnostic accuracy of RE in Gd-EOB-DTPA-enhanced liver MRI and hepatic fat fraction (HFF) in unenhanced liver MRI and ultrasound (US) for non-alcoholic fatty liver disease (NAFLD) screening in pediatric obesity. Seventy-four liver US and MRIs from 68 pediatric patients (13.07 ± 2.95 years) with obesity (BMI > BMI-for-age + 2SD) were reviewed with regard to imaging biomarkers (liver size, volume, echogenicity, HFF, and RE in Gd-EOB-DTPA-enhanced MRIs, and spleen size), blood biomarkers, and BMI. The agreement between the steatosis grade, according to HFF in MRI and the echogenicity in US, was moderate. Alanine aminotransferase correlated better with the imaging biomarkers in MRI than with those in US. BMI correlated better with liver size and volume on MRI than in US. In patients with RE < 1, blood biomarkers correlated better with RE than those in the whole sample, with a significant association between gamma-glutamyltransferase and RE ( p = 0.033). In conclusion, the relative enhancement and hepatic fat fraction can be considered as non-invasive tools for the screening and follow-up of NAFLD in pediatric obesity, superior to echogenicity on ultrasound.

Pediatric obesity has become in the last forty years the most common metabolic disease in children and adolescents affecting about 25% of the pediatric population in the western world. As obesity worsens, a whole-body insulin resistance (IR) occurs. This phenomenon is more pronounced during adolescence, when youth experience a high degree of insulin resistance due the production of growth hormone. As IR progresses, the blunted control of insulin on adipose tissue lipolysis causes an increased flux of fatty acids with FFA deposition in ectopic tissues and organs such as the liver, leading to the development of NAFLD. In this brief review, we will discuss the clinical implications of IR and NAFLD in the context of pediatric obesity. We will review the pathogenesis and the link between these two entities, the major pathophysiologic underpinnings, including the role of genetics and metagenomics, how these two entities lead to the development of type 2 diabetes, and which are the therapeutic options for NAFLD in youth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Barbieri, Santoro and Umano.)

Introduction: Thrombospondin 1 (THBS1) is a highly expressed adipokine in adults with obesity. In the present study, we aimed to investigate the clinical significance of THBS1in children with obesity and nonalcoholic fatty liver disease (NAFLD) and determine the effect of metformin on THBS1 expression in dietary-induced obese (DIO) mice., Methods: A cross-sectional study was conducted among 78 obese children and 35 nonobese children. Anthropometric parameters, clinical data, and circulating THBS1 levels were measured. The expression of THBS1 was detected in the serum and liver tissue from diet-induced obese mice (C57BL/6) with or without metformin treatment., Results: Higher THBS1 levels were observed in children with NAFLD and higher SDS-BMI. Individuals in the higher THBS1 quartile had a higher prevalence of hypo-high-density lipoprotein cholesterol (HDL-C). Logistic regression analysis showed a significant correlation between THBS1 and NAFLD, as well as between hip circumference and leptin levels. Receiver-operating characteristic (ROC) analysis revealed that THBS1 was a more sensitive predictor of NAFLD than leptin. Additionally, metformin ameliorated hepatic steatosis and decreased hepatic THBS1 expression in high-fat diet (HFD)-fed mice., Conclusions: Circulating THBS1 level may be a risk factor for NAFLD in obese children. Our findings provided a novel approach of metformin administration for the prevention and treatment of NAFLD. This study also confirmed that metformin decreased the expression of hepatic THBS in DIO mice., (© 2022 S. Karger AG, Basel.)

Background: Insulin resistance (IR), one of the key components of the metabolic syndrome, is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the relationship between surrogate markers of IR and the severity of NAFLD among overweight or obese children., Methodology: A total of 56 consecutive children aged 6 to 18 years old were recruited from the pediatric obesity and type 2 diabetes mellitus (T2DM) clinic in University Malaya Medical Centre (UMMC) from 2016 to 2019. Data on anthropometric measurements, clinical components of metabolic syndrome and fasting serum insulin were collected. Triglyceride to high-density lipoprotein cholesterol ratio (TG: HDL-C), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and Single Point Insulin Sensitivity Estimator (SPISE) were calculated. Transient elastography was performed with hepatic steatosis and liver fibrosis assessed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively., Results: A total of 44 children (78.6%) had liver steatosis and 35.7% had presence of significant liver fibrosis (stage F≥2). Majority (89.3%) are obese and 24 children (42.9%) were diagnosed with metabolic syndrome. Higher number of children with T2DM and significant liver fibrosis were associated with higher tertiles of TG: HDL-C ratio (p<0.05). Top tertile of TG: HDL-C ratio was an independent predictor of liver fibrosis (OR=8.14, 95%CI: 1.24-53.36, p=0.029). ROC analysis showed that the area under the curve (AUC) of HOMA-IR (0.77) and TG: HDL-C ratio (0.71) were greater than that of metabolic syndrome (0.70), T2DM (0.62) and SPISE (0.22). The optimal cut-off values of HOMA-IR and TG: HDL-C ratio for detecting liver fibrosis among children with NAFLD are 5.20 and 1.58, respectively., Conclusion: Children with NAFLD and higher TG: HDL-C ratio are more likely to have liver fibrosis. TG: HDL-C ratio is a promising tool to risk stratify those with NAFLD who are at risk of developing advanced liver disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ting, Jalaludin, Zaini and Mohamed.)

Background: Given the high prevalence of non-alcoholic fatty liver disease (NAFLD) in obese children, non-invasive markers of disease to date are still limited and worth exploring., Objective: This study aimed to evaluate the association between inflammatory markers and NAFLD in obese children., Methods: We performed a case-control study in Hunan Children's Hospital from September 2020 to September 2021. Study participants were children with obesity diagnosed with NAFLD by abdominal ultrasound examination. Mean platelet volume (MPV), platelet distribution width (PDW), neutrophil, lymphocyte, monocyte, and platelet counts were extracted from medical records and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression analysis was performed to evaluate the association between inflammatory markers and NAFLD. We also used receiver operating characteristic curve analysis to assess the discriminative ability of inflammatory cytokines for NAFLD., Results: Two hundred and sixty-seven obese children were enrolled, including 176 NAFLD patients and 91 simple obesity controls. Multivariable logistic model indicated that increased interleukin (IL)-1β [odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.04-1.27], IL-6 (OR = 1.28, 95% CI: 1.07-1.53), and IL-17 (OR = 1.04, 95% CI: 1.02-1.07) levels were significantly associated with NAFLD. In contrast, we observed non-significant associations for IL-8, IL-12, IL-21, IL-32, tumor necrosis factor-α (TNF-α), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), mean platelet volume (MPV), and platelet distribution width (PDW) with NAFLD. The area under the curves (AUCs) of IL-1β, IL-6, and IL-17 to discriminate obese children with or without NAFLD were 0.94, 0.94, and 0.97, respectively., Conclusions: Our results indicated that IL-1β, IL-6, and IL-17 levels were significantly associated with NAFLD. These inflammatory cytokines may serve as non-invasive markers to determine the development of NAFLD and potentially identify additional avenues for therapeutic intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Duan, Luo, Pan, Wei, Xiao, Li and Luo.)

The rise in prevalence of childhood obesity is paralleled by an increase in obesity-related metabolic complications, which add significantly to the population burden of cardiovascular morbidity in the long term. Early detection of obesity-related metabolic complications through appropriate screening strategies forms a crucial aspect of obesity management. We performed a scoping review of international and national guidelines on the management of pediatric obesity to evaluate the recommendations on screening for metabolic complications, namely, hypertension, diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Thirty guidelines were included, 23 (76.7%) of which had some guidance on screening for metabolic complications. However, there were significant variations in the extent and details of recommendations for screening for these metabolic complications. There has been no consensus on the body mass index (BMI) thresholds, age of onset, frequency, and screening tests recommended for detecting hypertension, diabetes, dyslipidemia, and non-alcoholic fatty liver disease between guidelines. These variations did not appear to be polarized based on geographical location or population ethnicity. We provide our recommendations on metabolic screening based on the strength of evidence in the guidelines, also incorporating recommendations from key childhood hypertension, diabetes, and lipid guidelines. Appropriate implementation of screening strategies is crucial to improve detection of metabolic complications, to allow for earlier or more intensified interventions for affected children with obesity., (© 2022 World Obesity Federation.)

Background: Although we know the key role of gut dysbiosis in nonalcoholic fatty liver disease (NAFLD), it remains unclear what microbe(s) are responsible. This study aims to identify the microbes that cause NAFLD., Methods: C57BL/6JNarl male mice fed a high-fat diet (HFD) were orally administered Lactobacillus reuteri (L. reuteri) or Lactobacillus rhamnosus GG plus Bifidobacterium animalis subsp. lactis BB12 (LGG plus BB12). Their fecal microbiomes identified by 16S rRNA sequencing were correlated with the severity of fatty liver. We then used a human cohort to confirm the role of the microbe(s). The HFD-fed mice were administrated with the identified bacterium, Desulfovibrio. The histopathological changes in the liver and ileum were analyzed., Results: Lactobacillus and Bifidobacterium improved hepatic steatosis and fibrosis in HFD-fed mice, which was related to the decreased abundance of Desulfovibrio in feces. Further human study confirmed the amount of D. piger in the fecal microbiota of obese children with NAFLD was increased. We then administered D. piger and found aggravated hepatic steatosis and fibrosis in HFD-fed mice. Hepatic expression of CD36 was significantly increased in HFD-fed mice gavaged with D. piger. In HepG2 cells, overexpression of CD36 increased lipid droplets, whereas knockdown of CD36 decreased lipid droplets. HFD-fed mice gavaged with D. piger had a decrease in the villus length, crypt depth, and zonula occludens-1 density in the ileum tissue., Conclusions: Our findings provide novel insights into the role of Desulfovibrio dysregulation in NAFLD. Modulation of Desulfovibrio may be a potential target for the treatment of NAFLD., (© 2022. Japanese Society of Gastroenterology.)

Objectives: Inflammation is a feature of non-alcoholic fatty liver disease progression and plays an important role in hepatic steatosis and fibrosis. Since there are no studies in the literature showing the relationship between hepatosteatosis with the systemic immune-inflammation index (SII) and pan-immune inflammation value (PIV), we aimed to evaluate the relationship between these biomarkers and hepatosteatosis in childhood., Methods: We included 133 consecutive obese children and adolescents aged 6-18 years into this single-center, retrospective, and cross-sectional study. Anthropometric, physical examination, radiological and laboratory data were obtained and recorded from the file records of each case., Results: When we grouped the patient population according to the grade of hepatosteatosis, there was a statistically significant difference between the groups in terms of SII and PIV values (p<0.05, for both). In the analyzes performed to identify independent predictors of hepatosteatosis pubertal status (p=0.019) and PIV value (p<0.001) were found to be significant as independent predictors. Moreover, in the analysis performed to predict severity of hepatic steatosis, regression analysis was performed by dividing the groups into groups with and without severe adiposity. As a result of this analysis, HOMA-IR (p=0.019) and PIV value (p=0.028) were found to be significant in the prediction of severe hepatic adiposity., Conclusions: Our findings showed that increased PIV levels were associated with the presence and severity of hepatic steatosis, but not with SII., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background & Aims: Childhood obesity, with associated comorbidities such as nonalcoholic fatty liver disease (NAFLD), is an increasing global health problem. Although lifestyle management is the mainstay of treatment, its efficacy on liver fibrosis has not yet been established., Methods: Children and adolescents admitted for severe obesity at a tertiary center (Zeepreventorium, De Haan, Belgium) were enrolled in this prospective study. Intensive lifestyle therapy encompassed caloric restriction, physical activity, education on a healthy lifestyle, and psychosocial support. At baseline, 6 months, and 12 months, liver ultrasound and transient elastography with controlled attenuation parameter were performed to assess liver steatosis and fibrosis., Results: A total of 204 patients (median age, 14.0 y; body mass index Z-score, +2.8) were evaluated at admission. NAFLD on ultrasound was present in 71.1%, whereas 68.6% had controlled attenuation parameter values of 248 dB/m or greater. A total of 32.8% of patients had at least F2 fibrosis, including 10.3% with transient elastography of 9 kPa or greater. After 6 months, the median body weight loss was 16.0% in the 167 patients evaluated. Fibrosis improved in 75.0% (P &lt; .001). Baseline severity of liver fibrosis and steatosis were predictors of fibrosis resolution. Seventy-nine patients had reached the 1-year time point. The improvements were sustained because fibrosis regressed at least 1 stage in all patients with baseline fibrosis. Fasting serum alanine aminotransferase and homeostasis model assessment of insulin resistance decreased significantly over the 1-year period (P &lt; .001)., Conclusions: NAFLD and associated fibrosis are highly prevalent in children and adolescents with severe obesity. An intensive multidisciplinary lifestyle management program that causes significant weight loss not only improves liver steatosis, but also fibrosis., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The early detection and management of children with metabolic associated fatty liver disease (MAFLD) is challenging., Objective: To develop a non-invasive and accurate prediction protocol for the identification of MAFLD among children with overweight/obesity candidates to confirmatory diagnosis., Methods: A total of 115 children aged 8-12 years with overweight/obesity, recruited at a primary care, were enrolled in this cross-sectional study. The external validation was performed using a cohort of children with overweight/obesity (N = 46) aged 8.5-14.0 years. MAFLD (≥5.5% hepatic fat) was diagnosed by magnetic resonance imaging (MRI). Fasting blood biochemical parameters were measured, and 25 candidates' single nucleotide polymorphisms (SNPs) were determined. Variables potentially associated with the presence of MAFLD were included in a multivariate logistic regression., Results: Children with MAFLD (36%) showed higher plasma triglycerides (TG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate transaminase (AST), glutamyl-transferase (GGT) and ferritin (p < 0.05). The distribution of the risk-alleles of PPARGrs13081389, PPARGrs1801282, HFErs1800562 and PNLPLA3rs4823173 was significantly different between children with and without MAFLD (p < 0.05). Three biochemical- and/or SNPs-based predictive models were developed, showing strong discriminatory capacity (AUC-ROC: 0.708-0.888) but limited diagnostic performance (sensitivity 67%-82% and specificity 63%-69%). A prediction protocol with elevated sensitivity (72%) and specificity (84%) based on two consecutive steps was developed. The external validation showed similar results: sensitivity of 70% and specificity of 85%., Conclusions: The HEPAKID prediction protocol is an accurate, easy to implant, minimally invasive and low economic cost tool useful for the early identification and management of paediatric MAFLD in primary care., (© 2022 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease among children with a higher prevalence among obese. Fatty liver index (FLI), an algorithm derived to screen NAFLD using the waist circumference, body mass index, triglyceride and gamma glutamyl-transferase concentration was rarely investigated in Asian paediatric population. Since each component is routinely measured in clinical practice, it is feasible to measure FLI even in resource limited settings. Hence, we determined the accuracy of FLI for the screening of NAFLD in obese children in Southern Sri Lanka., Methods: A descriptive cross sectional study was conducted on ninety five children (56 boys) aged 5-15 years with BMI ≥ 85th percentile for age and gender based on CDC 2000 growth charts recruited from the nutrition clinic at the Teaching Hospital, Karapitiya, Sri Lanka. NAFLD was diagnosed by ultrasonography. Factors associated with ultrasonographic fatty liver such as biochemical parameters and fatty liver index in either sex or the whole population were determined by a multivariate analysis. The ability of FLI to screen NAFLD was determined by the analysis of area under the receiver operator characteristic curve (AUROC) and the maximum Youden index analysis., Results: Overweight and obese children with ultrasonographic fatty liver had a significantly higher FLI than those without fatty liver according to the multivariate analysis performed (Odds ratio 3.524; 95% CI 1.104-11.256, P = 0.033). AUROC of FLI for NAFLD was 0.692 (95% CI; 0.565-0.786) and the optimal cut off value for the screening of NAFLD was 30 (Maximum Youden index 0.2782, Sensitivity, 58.33%; Specificity, 69.49%)., Conclusion: FLI could accurately be used in resource limited community settings and in epidemiological studies to screen overweight and obese children for NAFLD., (© 2022. The Author(s).)

Background: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver condition in the western world and is directly linked to obesity and the metabolic syndrome. Elevated body mass index is regarded as a major risk factor of NAFL (steatosis) and NAFLD fibrosis. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we sought to investigate whether other variables from adolescence could improve prediction of future NAFL and NAFLD fibrosis risk at 24 years, above BMI and sex., Methods: Aged 24 years, 4018 ALSPAC participants had transient elastography (TE) and controlled attenuation parameter (CAP) measurement using Echosens 502 Touch. 513 participants with harmful alcohol consumption were excluded. Logistic regression models examined which variables measured at 17 years were predictive of NAFL and NAFLD fibrosis in young adults. Predictors included sex, BMI, central adiposity, lipid profile, blood pressure, liver function tests, homeostatic model assessment for insulin resistance (HOMA-IR), and ultrasound defined NAFL at 17 years (when examining fibrosis outcomes). A model including all these variables was termed "routine clinical measures". Models were compared using area under the receiver operator curve (AUROC) and Bayesian Information Criterion (BIC), analysis, which penalises model complexity. Models were tested in all participants and those with overweight or obese standardised BMIs (BMI SDS) centiles at the 17-year time point. A decision curve analysis (DCA) was performed to evaluate the clinical utility of models in overweight and obese adolescents predicting NAFLD fibrosis at a threshold probability of 0.1., Results: The "routine clinical measures" model had the highest AUROC for predicting NAFL in all adolescent participants (AUROC 0.79 [SD 0.00]) and those with an overweight/obese BMI SDS centile (AUROC 0.77 [SD 0.01]). According to BIC analysis, insulin resistance was the best predictor of NAFL in all adolescents, whilst central adiposity was the best predictor in those with an overweight/obese BMI SDS centile. The "routine clinical measures" model also had the highest AUROC for predicting NAFLD fibrosis in all adolescent participants (AUROC 0.78 [SD 0.02]) and participants with an overweight/obese BMI SDS centile (AUROC 0.84 [SD 0.03]). However, following BIC analysis, BMI was the best predictor of NAFLD fibrosis in all adolescents including those with an overweight/obese BMI SDS centile. A decision curve analysis examining overweight/obese adolescent participants showed the model that had the greatest net benefit for increased NAFLD fibrosis detection, above a treat all overweight and obese adolescents' assumption, was the "routine clinical measures" model. However, the net benefit was marginal (0.0054 [0.0034-0.0075])., Conclusion: In adolescents, routine clinical measures were not superior to central adiposity and BMI at predicting NAFL and NAFLD fibrosis respectively in young adulthood. Additional routine clinical measurements do provide incremental benefit in detecting true positive fibrosis cases, but the benefit is small. Thus, to reduce morbidity and mortality associated with NASH cirrhosis in adults, the ultimate end point of NAFLD, the focus must be on obesity management at a population level., (© 2022. The Author(s).)

Objective: To investigate the utility of the controlled attenuation parameter (CAP), as measured by a liver elastography technique, in predicting varying degrees of liver steatosis in children with obesity., Methods: Children with obesity attending the pediatric obesity clinic at the Affiliated Hospital of Hangzhou Normal University from July 2020 to May 2021 were retrospectively analysed. The 71 subjects were divided into four groups according to the degree of liver steatosis obtained by magnetic resonance imaging-proton density fat fraction (MRI-PDFF). The gender, age, CAP, LSM, ALT, AST, BMI, uric acid, fasting blood glucose, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, insulin, and blood 25-hydroxyvitamin D levels of the four groups were compared, and the differences were analysed. Clinical data with significant differences were included in the logistic regression analysis. The receiver operating characteristic (ROC) curve for the CAP for the 71 subjects with different degrees of liver steatosis was plotted to evaluate the diagnostic value., Results: The 71 children were divided into groups according to the degree of hepatic steatosis obtained by MRI-PDFF, and the clinical data for each group were compared. It was found that there was statistical significance for CAP, ALT, and AST in cases of moderate and severe hepatic steatosis (p < 0.05). Logistic regression analysis was conducted between CAP, ALT, AST, and moderate to severe hepatic steatosis in children with obesity, and it was found that CAP was a factor related to moderate to severe hepatic steatosis in children with obesity. The ROC curve indicated that CAP has diagnostic value for NAFLD in children with obesity., Conclusion: There is diagnostic value in the use of CAP for hepatic steatosis in children with obesity, and there is greater diagnostic value in the use of CAP for children with moderate to severe hepatic steatosis., (© 2022 World Obesity Federation.)

Background: While for individuals with obesity an association between hyperleptinemia and an increased risk of non-alcoholic fatty liver disease (NAFLD) is assumed, a leptin deficiency is also related to the development of NAFLD early in life in ob/ob mice, in patients with leptin deficiency due to biallelic likely pathogenic variants in the leptin gene, and in patients with lipodystrophy., Objectives: To investigate the association of circulating leptin levels in pre-pubertal children with obesity and steatosis hepatis., Methods: The cross-sectional study consisted data of n=97 (n male =76) pre-pubertal children (11.8 ± 1.5 years) with obesity (BMIz: 2.4 ± 0.4). Fasting concentrations of cardiometabolic parameters were measured: insulin, c-peptide, glucose, triglyceride, cholesterol, HDL, LDL, AST, ALT, GGT, leptin. Steatosis hepatis was diagnosed by an ultrasound examination (mild, moderate or severe). Patients were categorized into two groups: low z-score of circulating leptin levels (≤25th percentile) vs. normal z-score of circulating leptin levels., Results: One-third of the children with obesity were diagnosed with steatosis hepatis (I°: 63.6%, II°/III°: 36.4%). Children with steatosis hepatis had significantly lower z-scores of circulating leptin levels compared to children with an unremarkable liver ultrasonography (-2.1 ± 0.8 vs. -0.7 ± 0.6). Z-scores of circulating leptin levels correlate negatively with degree of steatosis hepatis. Children with low z-scores of circulating leptin levels had significantly higher triglyceride, fasting insulin and c-peptide levels compared to children with normal z-scores of circulating leptin levels., Conclusion: Prepubertal children with NAFLD and obesity and partial leptin deficiency might be defined as a clinical subgroup., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brandt, von Schnurbein, Denzer, Kratzer and Wabitsch.)

Objective: To determine the relationship between lipid profile and non-alcoholic fatty liver disease in obese children and adolescents., Study Design: A comparative cross-sectional study., Place and Duration of Study: Department of Pediatrics, Kastamonu Training and Research Hospital, Turkey, from March 2018 to April 2021., Methodology: Clinical, laboratory and ultrasound findings of 290 children and adolescents diagnosed with obesity were analysed. Children and adolescents were divided into two groups as those who were diagnosed with NAFLD by ultrasonography (USG) and those who did not were diagnosed. Two groups were compared in terms of clinical and biochemical findings., Results: The body mass index (BMI), bodyweight for height (BWH), insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), free T4, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), hemoglobin A1c (HbA1c) and HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) levels were found to be significantly higher (p<0.05) in the children and adolescents with NAFLD In obese children and adolescents; there was a significant correlation between the increase in TC, LDL-C and TG levels in the blood and the development of NAFLD (p<0.05). Blood ALT level ≥37 U/L in obese boys and ≥23.5 U/L in obese girls was found to be a strong diagnostic biomarker in determining the presence of NAFLD., Conclusion: In obese children and adolescents, there was a significant relationship between the increase in BWH and blood lipid levels, insulin resistance and the development of NAFLD. ALT had high specificity and sensitivity to predict non-alcoholic fatty liver disease., Key Words: Obesity, Children, Hepatosteatoz.

Not all children with obesity carry a similar risk of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of obesity severity, metabolic risk parameters, and obesity treatment outcome on later risk of NAFLD in paediatric obesity. We conducted a nested case-control study of children and adolescents enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) (2001-2016). NAFLD was ascertained from the National Patient Register. Five controls per case were matched by sex and age at index date and at the obesity treatment initiation. Seventy-six pairs (n cases = 76, n controls = 241) were included in the analysis (29% females, mean age at obesity treatment initiation was 10.8 ± 3.07 years). Mean age of NAFLD diagnosis was 14.2 ± 3.07 years. The risk for NAFLD increased with severe obesity (odds ratio [OR]: 3.15, 95% confidence interval [CI]: 1.69-5.89), impaired fasting glucose (OR: 5.29, 95% CI: 1.40-20.06), high triglycerides (OR: 2.33, 95% CI: 1.22-4.43) and weight gain (OR: 4.67, 95% CI: 1.51-14.49 per body mass index standard deviation score [BMI SDS] unit). Relative weight loss of at least 0.25 BMI SDS units reduced NAFLD risk independently of other risk factors (OR: 0.09, 95% CI: 0.01-0.56). Severe obesity, impaired fasting glucose and high triglycerides are risk factors for future NAFLD in paediatric obesity. Successful obesity treatment almost eliminates the risk for NAFLD independently of obesity severity, IFG and high triglycerides., (© 2021 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Non-alcoholic fatty liver disease (NAFLD) has become the most common causes of liver disease in children and adolescents. Although several reports have confirmed the significant correlation between NAFLD and growth hormone (GH)-insulin-like growth factor 1(IGF-1) axis, no study further investigates whether or not recombinant human GH (rhGH) treatment can improve NAFLD in obese children., Methods: This study was a randomized, open-label study comprising 44 boys with obesity and NAFLD (11.76 ± 1.67 year) to evaluate the effects of 6 months of rhGH administration for boys with obesity and NAFLD. The subjects were randomized divided into treatment group (subjects with recombinant human GH (rhGH)) and control group for 6 months., Results: After 6 months, IGF-1 increased significantly during rhGH treatment, in comparison with the control group (582.45 ± 133.00 vs. 359.64 ± 129.00 ng/ml; p < 0.001). A significant reduction in serum alanine aminotransferase(ALT) (15.00 vs. 28.00 U/L; p = 0.001), aspartate aminotransferase(AST) (20.00 vs. 24.50U/L; p = 0.004), gamma glutamyl transferase(GGT) (14.50 vs. 28.50 U/L; p < 0.001) was observed in the GH-treated boys. In addition, the rhGH group showed a significant decrease in C reactive protein (CRP) (1.17 ± 0.76 vs. 2.26 ± 1.43 mg/L) and body mass index standard deviation scores (BMI SDS) (2.28 ± 0.80 vs. 2.71 ± 0.61) than the control group (p = 0.003, p = 0.049 respectively). GH treatment also reduced low density lipoprotein cholesterol (LDL-C) (2.19 ± 0.42 vs. 2.61 ± 0.66 mmol/L; p = 0.016) and increased high density lipoprotein cholesterol (HDL-C) (1.30 vs. 1.15 mmol/L; p = 0.005), and there were no changes in total cholesterol (TC), triglycerides (TG) and uric acid(UA) between the treatment group and the control group., Conclusion: Our findings suggest that 6 months treatment with rhGH may be beneficial for liver enzyme and can improve obesity-related other cardiovascular and metabolic complications in boys with obesity and NAFLD., (© 2022. The Author(s).)

Objectives: It has been suggested that circulating fatty acids (FAs) take part in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in children with obesity. The aims of this study were to evaluate the serum FA concentration in this pediatric population., Methods: The prospective study included 80 children with obesity and suspected liver disease. Patients with viral hepatitis, autoimmune, toxic, and selected metabolic liver diseases were excluded. Criteria for NAFLD diagnosis included liver steatosis in ultrasound as well as elevated alanine transaminase (ALT) serum activity. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1H-MRS). Fasting serum FA concentrations were measured in all children using gas-liquid chromatography., Results: NAFLD was diagnosed in 31 children. Total FA concentration was significantly higher (P < 0.01) in all obese children as well as in obese children with NAFLD compared with controls. In children with NAFLD, a significant, positive correlation was found between total FA concentration and cholesterol (R = 0.47, P < 0.01), triacylglycerols (R = 0.78, P < 0.001), and insulin (R = 0.45, P < 0.011). In a group of children with obesity, TILC correlated positively with saturated FA concentration (R = 0.23, P < 0.05)., Conclusion: Data from the present study do support the hypothesis that FAs are potentially involved in the pathogenesis of NAFLD in children with obesity., (Copyright © 2021 Elsevier Inc. All rights reserved.)